Polyarthritis As a Prewarning Sign of Occult Lung Cancer

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provided by Elsevier - Publisher Connector Kaohsiung Journal of Medical Sciences (2012) 28,54e56

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CASE REPORT Polyarthritis as a prewarning sign of occult lung cancer

Yong-Mei Han a, Li-Zheng Fang a, Xin-Hua Zhang a,*, Shi-Hai Yuan a, Jian-Hua Chen a, You-Ming Li b

a Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China b Department of Gastroenterology, The First Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Received 9 September 2010; accepted 27 December 2010 Available online 11 December 2011

KEYWORDS Abstract Cancer polyarthritis is an uncommon, paraneoplastic manifestation of some solid Lung cancer; and hematological malignancies. Herein, we report the case of a 55-year-old woman who Paraneoplastic recently experienced polyarthritis for 2 months. On admission, the patient developed cough, syndrome; expectoration, and fever. According to the clinical manifestations and the ﬁndings in radiolog- Polyarthritis ical examinations and sputum cultures, pneumonia was considered. No evidence of lung cancer was noted by repeated computed tomography scan of lung, single bronchoscopy, or computed tomographyeguided lung biopsy. Ultimately, the second bronchoscopy with biopsy was carried out, and lung adenocarcinoma was conﬁrmed by pathological examination. Symptoms of polyarthritis starting 2 months before the symptoms of her lung cancer in the present case leads us to believe that polyarthritis may be a manifestation of paraneoplastic syndrome. Arthritis resolved after anticancer therapy. Our report indicates that polyarthritis of unknown cause may be suspected as a manifestation of malignancies. Copyright ª 2011, Elsevier Taiwan LLC. All rights reserved.

Introduction Polyarthritis is a common disease but polyarthritis as a primary manifestation is relatively rare in malignancies. In Neoplasms may present characteristics of rheumatic disor- this case, we report about a Chinese woman who recently ders [1]. Some of the rheumatological manifestations may experienced polyarthritis for 2 months, and ﬁnally, lung result from direct cancer invasion or metastasis into bone cancer was diagnosed. Our report may be helpful for timely and joints, which are occasionally absent in some cases [2]. diagnosis and treatment of occult cancers.

* Corresponding author. Department of General Practice, Sir Run Case presentation Run Shaw Hospital, School of Medicine, Zhejiang University, No. 3 East Qingchun Road, Hangzhou 310016, China. In November 2009, a 55-year-old woman came to our E-mail address: [email protected] (X.-H. Zhang). outpatient clinic with the complaint of gradually worsening

1607-551X/$36 Copyright ª 2011, Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.kjms.2011.06.035 Polyarthritis and occult lung cancer 55 polyarthritis for 2 months. Two months earlier, she presented with right knee pain. Three days later, the pain was also felt in her right shoulder, with subsequent involvement of her wrists, bilateral metacarpophalangeal joints (MCP), and elbows. Swellings of bilateral MCPs and wrists occurred several days later. Symptoms did not improve after activity or rest. No joint stiffness, subcutaneous nodules, respiratory symptoms, or fever was presented. She also denied diarrhea, frequent urination, or dysuria before the joint pain. In other hospitals, laboratory examinations of rheumatoid factor (RF), antinuclear antibodies, uric acid, HLA- B27, immunoglobulin, and complements showed normal results, and symptoms were not alleviated after adminis- tration of nonsteroidal anti-inflammatory drugs. She lost appetite and weight of 5 kg in 2 months. The patient was a nonsmoker and never consumed alcohol. There was no Figure 1. Chest computed tomography showed inflammation history of rheumatic diseases in her family members. in the anterior segment of bilateral upper lobes. On admission, physical examination, including those of calcoaceticus-baumannii in sputum culture. The patient’s skin, nails, fingers, toes, and genitals, revealed normal body temperature returned to normal 1 week later, but she results except tenderness and swelling of bilateral MCPs developed chest tightness and shortness of breath on and wrists, and pretibial tenderness was not found. Labo- exercise. Chest CT showed that the lesions in the right lung ratory examinations revealed the following: erythrocyte were improved, but those in the left lung remained. Left sedimentation rate, 44 mm/hr (range, 1e20 mm/hr); lung biopsy was carried out under the guidance of CT, and immunoglobulin G, 1,970 mg/dL (range, 694e1,620 mg/ the inflammatory lesion was confirmed. Because the dL); carcinoma embryonic antigen (CEA), 11.96 ng/mL symptoms were not relieved significantly, the patient was (range, 0e5 ng/mL); and ferritin, greater than 2,000 mg/L treated with intravenous infusion of voriconazole (Pfizer (range, 13e150 mg/L). RF, HLA-B27, antinuclear antibodies, Ireland Pharmaceuticals Limited, Ireland) (200 mg, bid) for anti-streptolysin O, high-sensitivity C-reactive protein, 10 days according to the sputum smears positive for fungi. blood cell count, and kidney and liver function parameters However, the patient’s condition worsened and joint pain were all within normal ranges. Magnetic resonance imaging progressed, and it was more serious than before. Then, the of right knee indicated the degeneration of posterior horn fourth thoracic CT was performed, and progression of of the meniscus. Radiographic examination of both hands lesions in the left lung was indicated. Furthermore, serum showed normal results, and periosteum hypertrophy of the CEA was elevated to 23.37 ng/mL. The second bronchos- distal part of ulna and radius was not detected. Chest X-ray copy also revealed no neoplasm in the bronchus. Bronchial showed increased pulmonary markings with a suspicious brushing cytology showed negative result for malignancy. nodule in the right upper lung. Computed tomography (CT) Ultimately, the patient was diagnosed with adenocarci- of the lung documented inflammation in the lingular noma in the left lung according to pathological examination segment of left lung and subpleural pneumonia. by second bronchoscopy with biopsy (Fig. 2). Connective tissue diseases were suspected, and the Emission CT was performed, and no osseous metastasis patient was treated with diclofenac diethylamine emulgel was detected. After treatment with gefitinib tablet (Beijing Novartis Company, China), but the pain or swelling (AatraZeneca Pharmaceuticals, England) (250 mg, once of the joints did not resolve. On the fourth day of admis- a day (qd)), cough, chest tightness, and shortness of breath sion, the patient complained of cough with sputum. Fine were improved significantly, and the pain and swelling of moist rales were heard at bilateral lower lobes. According the joints alleviated accordingly. to the clinical manifestations and the findings on imaging, pneumonia was considered. She was treated with intravenous infusion of cefuroxime (GlaxoSmithKline S.p.A., Italy) Discussion (1.5 g, twice a day (bid)) and ambroxol tablet (Boehringer Ingelheim Corporate, German) (30 mg, three times a day The causes of cancer-associated rheumatic disorders can be (tid)). Despite 7 days of antibiotic treatment, cough and classified as follows [3]: direct invasion by cancer; para- expectoration persisted, and the patient developed a fever neoplastic syndromes; altered immune surveillance, of 38.5C. Chest CT showed inflammation in the right upper resulting in both the rheumatic and the neoplastic diseases; and middle lobes and the left upper and lower lobes, and adverse effects of anticancer therapy. Paraneoplastic a small amount of bilateral pleural effusion and mediastinal rheumatic disorders are those cancer-associated rheumatic lymph node enlargement (Fig. 1). Bronchoscopy revealed syndromes occurring at a distance from the primary cancer no abnormalities. The laboratory findings were as follows: site or as a result of metastasis and are mediated by leukocyte count, 4.2/nL (range, 4.0e10.0/nL); neutrophils, humoral factors (hormones or cytokines) excreted by tumor 77.7% (range, 55e75%); C-reactive protein, 8.71 mg/L cells or by an immune response against the tumor. Poly- (range, 0e5 mg/L); and erythrocyte sedimentation rate, arthritis can be a manifestation of paraneoplastic syndrome 53 mm/hr. The patient was treated with intravenous infu- and is associated with various malignancies. sion of imipenem (Merck & Co., inc., U.S.A) (0.5 g, every 8 Cancer polyarthritis is an uncommon clinical entity, but hours) because of the positivity for Acinetobacter its recognition is of clinical importance because its 56 Y.-M. Han et al.

paraneoplastic syndrome. The present case is consistent with the findings that cancer polyarthritis is characterized by the late onset of disease, explosive nature of arthropathy, severity of pain disproportionate to physical findings, absence of RF or rheumatoid nodules, no family history of rheumatoid arthritis, and absence of lesions on radiography [4,5]. In our case, the involvement of bilateral wrist and MCP joints of hands was noted. Further examinations estab- lished the diagnosis of lung adenocarcinoma, and the polyarthritis was considered as a presentation of paraneoplastic syndrome. The fact that arthritis resolved significantly after anticancer therapy further confirmed the diagnosis of cancer polyarthritis. In the present case, weight loss was complained of. Systemic symptoms may be early manifestations of occult neoplasia, and the cause of systemic symptoms should be identified, which may be beneficial for the identification of underlying malignancies. CEA is one of the tumor markers. In our case, CEA was elevated before the respiratory manifestations and increased gradually. Finally, lung adenocarcinoma was detected. Cancer polyarthritis may develop before the occurrence of obvious symptoms of malignancies [6]; thus, arthropathy of unknown cause accompanied with increased CEA level should be suspected as cancer polyarthritis, and related cancers should be screened. Thereafter, close follow-up is necessary to exclude or confirm the diagnosis of malignancies, espe- cially when the CEA level increased gradually. In conclusion, cancer polyarthritis is a relatively rare phenomenon, to which one needs to pay enough attention. Cancer polyarthritis should be considered in patients pre- senting polyarthritis of uncertain cause, and sometimes, repeated examinations are necessary. Furthermore, the clinical course of a paraneoplastic syndrome usually Figure 2. Hematoxylin and eosin staining and light micros- parallels with the progression of the malignancy. Once the copy of lung tissue. Cancer cells were arranged in solid nests or association between a malignancy and a paraneoplastic cords, and a fraction of cancer cells showed a tubule-like syndrome is identified, reappearance of symptoms can be growth pattern. The cancer cells were atypical with frequent used to monitor cancer recurrence at an early stage [7]. mitotic figures. (A) 100Â; (B) 400Â. appearance may be a prewarning sign of occult neoplasia, References just as in the present case. Therefore, if appreciated, it may allow earlier cancer detection; if unrecognized, it may [1] Caldwell DS, McCallum RM. Rheumatologic manifestations of lead to misdiagnosis and poor prognosis. cancer. Med Clin North Am 1986;70:385e417. The clinical features of the present patient illustrate [2] Butler RC, Thompson JM, Keat ACS. Paraneoplastic rheumatic disorder: a review. J R Soc Med 1987;80:168e71. a few interesting points. The patient initially presented [3] Naschitz JE, Rosner I, Rozenbaum M, Zuckerman E, Yeshurun D. with polyarthritis, but was free of respiratory symptoms. Rheumatic syndromes: clues to occult neoplasia. Semin Subsequently, this patient developed cough, expectora- Arthritis Rheum 1999;29:43e55. tion, and fever, and pneumonia was considered. No [4] Stummvoll GH, Aringer M, Machold KP, Smolen JS, Raderer M. evidence of lung cancer was demonstrated by repeated CT Cancer polyarthritis resembling rheumatoid arthritis as a first scan, bronchoscopy, and lung biopsy. Progression of symp- sign of hidden neoplasms. Report of two cases and review of toms even after anti-infection treatment and findings on the literature. Scand J Rheumatol 2001;30:40e4. imaging made the diagnosis of pneumonia uncertain. Thus, [5] Naschitz JE. Rheumatic syndromes: clues to occult neoplasia. bronchoscopy was carried out again, and lung adenocarci- Curr Opin Rheumatol 2001;13:62e6. noma was confirmed by the pathological examination. It [6] Kumar S, Sethi S, Irani F, Bode BY. Anticyclic citrullinated peptide antibody-positive paraneoplastic polyarthritis in indicates that a malignancy may be suspected when poly- a patient with metastatic pancreatic cancer. Am J Med Sci arthritis of unknown cause is present, even in the absence 2009;338:511e2. of common manifestations of malignancies. [7] Bivalacqua TJ, Alphs H, Aksentijevich I, Schaeffer EM, Symptoms of polyarthritis started 2 months before the Schoenberg MP. Paraneoplastic polyarthritis from non-small- symptoms of her lung cancer in the present case, which led cell lung cancer metastatic to the bladder. J Clin Oncol 2007; us to believe that polyarthritis may be a manifestation of 25:2621e3.